Cancer of the colon is the second most prevalent malignancy in the U.S. There is strong evidence that adenomatous colon polyps are precursor lesions of colon cancer. Such polyps are found in up to 40% of persons over age 50. It has recently been confirmed that certain non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin synthesis, can inhibit the formation of polyps and cancers in animals, cause reproducible changes in mucosal markers for cancer and cause regression of polyps in people with genetic polyposis-syndromes. The aims of this proposal are to determine: 1) If therapy with sulindac (a NSAID) causes regression of sporadically occurring colorectal adenomas, 2) If sulindac therapy causes consistent changes in intermediate markers of colorectal cancer (PGE2, BrdU incorporation, PCNA), 3) To examine the feasibility of, and establish the mechanism for, a similar phase III study based on the results of this project. This phase II study is to be a randomized, double blind, placebo-controlled trial with 2 treatment groups using different dosing schedules. A collaborative effort combining the extensive experience of the clinical investigators at the University of Utah and the outstanding achievements of basic scientists at the University of Arizona make this proposal sound, efficient and timely.